View source for 6emo


==Solution structure of the LEDGF/p75 IBD - JPO2 (aa 1-32) complex==
<StructureSection load='6emo' size='340' side='right'caption='[[6emo]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6emo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EMO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6emo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6emo OCA], [https://pdbe.org/6emo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6emo RCSB], [https://www.ebi.ac.uk/pdbsum/6emo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6emo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4.
== Function ==
[https://www.uniprot.org/uniprot/CDA7L_HUMAN CDA7L_HUMAN] Plays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter. Plays an important oncogenic role in mediating the full transforming effect of MYC in medulloblastoma cells. Involved in apoptotic signaling pathways; May act downstream of P38-kinase and BCL-2, but upstream of CASP3/caspase-3 as well as CCND1/cyclin D1 and E2F1.<ref>PMID:15654081</ref> <ref>PMID:15994933</ref> <ref>PMID:16829576</ref> [https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.

Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.,Sharma S, Cermakova K, De Rijck J, Demeulemeester J, Fabry M, El Ashkar S, Van Belle S, Lepsik M, Tesina P, Duchoslav V, Novak P, Hubalek M, Srb P, Christ F, Rezacova P, Hodges HC, Debyser Z, Veverka V Proc Natl Acad Sci U S A. 2018 Jul 11. pii: 1803909115. doi:, 10.1073/pnas.1803909115. PMID:29997176<ref>PMID:29997176</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6emo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Veverka V]]